Proteomics

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Targeted mass spectrometry enables multiplexed quantification of immunomodulatory proteins in clinical biospecimens


ABSTRACT: Immunotherapies are revolutionizing cancer care, producing durable responses and potentially cures in a subset of patients. However, response rates are low for most tumors, grade 3/4 toxicities are not uncommon, and our current understanding of tumor immunobiology is incomplete. While hundreds of immunomodulatory proteins in the tumor microenvironment shape the anti-tumor response, few of them can be reliably quantified. To address this need, we developed a multiplex panel of targeted proteomic assays to 52 peptides representing 46 proteins using peptide immunoaffinity enrichment coupled to multiple reaction monitoring-mass spectrometry. We validated the assays in tissue and plasma matrices, where performance figures of merit showed over 3 orders of dynamic range and median inter-day CVs of 5.2% (tissue) and 21% (plasma). A feasibility study in clinical biospecimens showed detection of 48/52 peptides in frozen tissue and 38/52 peptides in plasma. The assays are publicly available as a resource for the research community.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jeff Whiteaker  

PROVIDER: PXD029167 | panorama | Mon Feb 28 00:00:00 GMT 2022

REPOSITORIES: PanoramaPublic

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Targeted Mass Spectrometry Enables Multiplexed Quantification of Immunomodulatory Proteins in Clinical Biospecimens.

Whiteaker Jeffrey R JR   Lundeen Rachel A RA   Zhao Lei L   Schoenherr Regine M RM   Burian Aura A   Huang Dongqing D   Voytovich Ulianna U   Wang Tao T   Kennedy Jacob J JJ   Ivey Richard G RG   Lin Chenwei C   Murillo Oscar D OD   Lorentzen Travis D TD   Thiagarajan Mathangi M   Colantonio Simona S   Caceres Tessa W TW   Roberts Rhonda R RR   Knotts Joseph G JG   Reading Joshua J JJ   Kaczmarczyk Jan A JA   Richardson Christopher W CW   Garcia-Buntley Sandra S SS   Bocik William W   Hewitt Stephen M SM   Murray Karen E KE   Do Nhan N   Brophy Mary M   Wilz Stephen W SW   Yu Hongbo H   Ajjarapu Samuel S   Boja Emily E   Hiltke Tara T   Rodriguez Henry H   Paulovich Amanda G AG  

Frontiers in immunology 20211111


Immunotherapies are revolutionizing cancer care, producing durable responses and potentially cures in a subset of patients. However, response rates are low for most tumors, grade 3/4 toxicities are not uncommon, and our current understanding of tumor immunobiology is incomplete. While hundreds of immunomodulatory proteins in the tumor microenvironment shape the anti-tumor response, few of them can be reliably quantified. To address this need, we developed a multiplex panel of targeted proteomic  ...[more]

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